Surgery, chemotherapy and radiation therapy are the mainstay of cancer treatment and management. Surgery and radiation therapy are typically used to achieve results locally, whereas chemotherapy exerts a more systemic effect. Low to intermediate doses of cyclophosphamide are routinely used in combination chemotherapy for treating various types of cancers and appears to work either by stopping the growth of cancer cells or by killing the cancer cells. However, usually remaining cancer cells are able to divide, thereby leading to a relapse of the cancer. Accordingly, despite the use of combination chemotherapy to treat various types of cancers, a significant number of cancers remain incurable.
More recently, immunotherapy based techniques have been developed for the treatment of various cancers. The central premise underlying immunotherapy for cancer is the presence of antigens which are selectively or abundantly expressed or mutated in cancer cells. For example, active immunotherapy involves delivering an antigen associated with a cancer to a patient, such that the patient's immune system elicits an immune response against the antigen and consequently, against the cancer cells expressing the antigen. Passive immunotherapy, on the other hand, involves administering immune therapeutics such as, for example, an antibody which selectively binds an antigen expressed on a cancer cell.
Despite the advances in the development of various immune therapies for treatment of cancer, immune tolerance presents a major barrier. Therefore, there is a need to identify therapies or agents which may be used to break immune tolerance which severely limits the use of various immune therapies in cancer therapy.